[unreadable] A unique confluence of expertise in the areas of evolutionary/ comparative and theoretical immunobiology currently exists among the community of scholars working in New Mexico. The primary goal of this proposal is, through the opportunities provided by the COBRE program; establish a research center at the University of New Mexico with a thematic focus in these disciplines. The center will strengthen the ties among these senior investigators and so create a nurturing and vibrant environment where junior scholars with interests in theoretical and evolutionary immunobiology can prosper intellectually and become independently funded to pursue their interests in this area. This proposal builds on a tangible commitment made by the Department of Biology at UNM to strengthen this research area, and will foster increased connectivity with outstanding investigators with similar interests in University of New Mexico (UNM) Department of Computer Science and the Los Alamos National Laboratories (LANL). The Santa Fe Institute (SFI), located midway between UNM and LANL, has in the past fostered close ties between the mentors and will serve as a venue for many programmatic events. Evolutionary and theoretical aspects of immunology increasingly need to lie within the purview of the NIH. Indeed, there is a growing awareness of the great value of a solid theoretical basis for understanding how host defense systems work when confronted with infectious organisms or neoplasia. Also, our understanding of the important but neglected field of innate immunity, including human innate immunity, has been significantly advanced by discoveries made with fruit flies, pointing out the value of comparative models in illuminating the functions of mammalian immune systems. We seek to create an environment that regularly brings theoreticians and empiricists together, thus gaining new theoretical and historical perspectives on how immune systems evolve, and how sustainable and effective defense from pathogens is achieved. This program features four projects by outstanding and eligible investigators who are currently in place. It will also enable us to hire new faculty members to gain additional critical mass in these research areas, and provides urgently needed funds to strengthen the research infrastructure for our investigators. The research areas outlined are recognized by the scientific community as exciting and important. New Mexico has a growing reputation of leadership in these areas, and they present a novel opportunity to promulgate an ascendant field in which New Mexicans can define the cutting edge and that can not be easily duplicated anywhere else in the world. [unreadable] [unreadable]